2004, Master of Science in Pharmaceutical Sciences, University of Toledo, Pharmaceutical Science.

Abstract

It has been recently documented that subchronic exposure of rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)causes oxidative damage in various brain regions. In this study, we have investigated the effects of TCDD on the levels of biogenic amines in the rat brain after subchronic exposure. The rats were exposed to TCDD for 13 weeks at 2 different concentrations (22 and 46 ng/kg/day). At the end of the exposure period the animals were euthanized and brain tissue samples were collected from 4 different brain regions: Hippocampus (H), Cerebral Cortex (Cc), Midbrain (MB), and Cerebellum (C). These samples were kept at -80°C. These tissue samples were analyzd for different biogenic amines including NE, DA, DOPAC, 5-HIAA, 5-HT and HVA using a high performance liquid chromatography system with an electrochemical detector. The results show significant increases in DA, DOPAC and HVA in the hippocampus and cerebral cortex but not in the midbrain or the cerebellum in response to the 22 and 46 ng/kg/day doses. However, NE was significantly increased in the hippocampus and cerebral cortex in rats treated with 46 ng/kg/day, it was also increased in the midbrain and cerebellum at both the 22 and 46 ng/kg/day doses. These results are important since many of the TCDD-induced neurotoxic effects in humans are associated with functions of the brain regions found to be affected in this study.